Sabra Klein came to the annual meeting of the Society for the Study of Reproduction this week armed with a message that might seem obvious to scientists who obsess over sex: men and women are different. But it is a fact often overlooked by health researchers, says Klein, an immunologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.

Her research on influenza viruses in mice, presented at the meeting in Montreal, Canada, helps explain why women are more susceptible to death and disease from infectious pathogens — and the reason is intimately linked with reproduction. “She’s one of the people that really gets the bigger picture as far as why do we see these patterns,” says Marlene Zuk, an evolutionary biologist at the University of Minnesota, Twin Cities, in St. Paul.

Women generally suffer more severe flu symptoms than men, for example, despite the fact that they tend to have fewer viruses during an infection. To Klein, this suggests that women quickly mount a substantial immune-system attack to clear infections — and suffer the consequences of the inflammatory responses that flood their systems. “This is where females run into trouble,” Klein says.

Hormone replacement
She and her collaborators have found this disparity in mice infected with flu viruses. But when the researchers castrated the males and removed the ovaries from the females, the difference disappeared as the males became more sensitive to infection.

But testes are not simply protective. Klein found that giving the neutered females the female sex hormones oestrogen and progesterone actually protected them from disease.

For females, infections appear to throw these cycling sex hormones out of whack. They elongate the oestrus cycle in non-neutered female mice — stretching the part of the cycle associated with the lowest amounts of oestrogen from 4-5 days to 8-9 days.

Researchers have long known that immunological cells have receptors for sex hormones, and that autoimmune disease strikes women more frequently than men. Nevertheless, Klein says that her work should have implications for current public-health practices.

Women, who are often less likely than men to get vaccinated against flu, should be encouraged to do so, she says. And researchers may want to examine whether hormone-replacement therapies and contraceptive drugs have unintended — possibly positive — effects on some types of infectious disease.

But most importantly, Klein says, medical studies should take sex differences into account. Many epidemiological studies do not break down results by sex, a practice that she has found can obscure crucial trends. And clinical trials have traditionally worked around the female oestrus cycle, because it can interfere with results.

To Zuk, Klein has provided a voice of reason here. “Why is it viewed as interference when you have interaction with the endocrine system or some other aspect of the reproductive system?” she asks.

“The age-old answer we get is that funding is tight and if we’re going to compare sexes, we’ll have to double the groups,” says Klein. But on the basis of her work, she says, “I don’t know that that’s actually true”.

This article is reproduced with permission from the magazine Nature. The article was first published on July 26, 2013.